An in-vitro vascularized micro-tumor model of cervical cancer

Cervical cancer is a significant global health burden, ranking as the fourth most common cancer in women worldwide, with approximately 660,000 new cases each year, the majority of which occur in low- and middle-income countries. Despite the availability of preventive screening and HPV vaccination, cervical cancer remains a leading cause of cancer-related deaths, particularly in cases of advanced or recurrent disease. Current standard of care treatment approaches rely on a combination of cisplatin-based chemotherapy and radiotherapy. However, treatment resistance and disease recurrence continue to pose major challenges, underscoring the critical need for improved therapeutic strategies and more predictive preclinical models. Currently, up to 95% of drugs that show promise in preclinical trials fail to receive FDA approval due to poor efficacy and tumor resistance. These high failure rates can be attributed to unphysiological testing conditions neglecting the tumor microenvironment, as well as poor model systems failing to predict drug-induced pharmacological responses in the human body. To address these shortcomings in cervical cancer research and reliably predict the efficacy of drugs intended for human use, we have invented a novel organ-on-a-chip platform called the vascularized micro-tumor (VMT). The VMT microfluidic device allows for the de novo formation of micro-vessels, which are cocultured with cancer cells and associated stroma. Critically, the micro-vessels enable the physiological delivery of nutrients, drugs and immune cells into the complex 3D tumor microenvironment and hence constitute a powerful tool for physiological disease modeling and drug screening approaches. Here, we present the establishment of a cervical cancer VMT model based on well-characterized, commercially available tumor cell lines and demonstrate treatment responses to standard of care cisplatin-based chemotherapy and radiotherapy.